Aim: We aimed to compare the efficacy and safety of mini-percutaneous nephrolithotomy (mPNL) and standard PNL (sPNL) in a group of patients who had a history of PNL and/or open renal surgery (secondary patients). Materials and Methods: The study included 148 patients who underwent secondary PNL between November 2016 and September 2018. The patients with kidney stone >= 2 cm were included in the study. Patients were randomly divided into two groups as mPNL and sPNL. For both groups, demographic data, stone characteristics, and operative and postoperative data were recorded prospectively. Data were analyzed at 95% confidence interval and considered significant when p value was Results: A total of 148 (76 mPNL, 72 sPNL) patients with a history of PNL and/or open surgery were included in the study. The mean duration of operation was longer in mPNL (106.9 vs 91.2 minutes, p = 0.016). The mean duration of fluoroscopy in mPNL was shorter (4.4 vs 5.3 minutes, p = 0.021). The tubeless procedure was higher in the mPNL (21.1% vs 2.8%, p = 0.001). The hemoglobin drop was less in mPNL (0.7 vs 1.4 g/dL, p = 0.011). Duration of nephrostomy and hospitalization was longer in sPNL (p = 0.001 and p = 0.005, respectively). The success rate in the mPNL group was higher compared with the sPNL group; however, this difference was statistically insignificant (75.0% vs 72.2%, p = 0.558). Conclusion: mPNL is superior to sPNL in terms of hemoglobin drop, duration of fluoroscopy, applicability of a tubeless procedure, and duration of nephrostomy and hospitalization among secondary patients. Duration of operation was found to be longer for mPNL. Success rate was higher in the mPNL group, although not statistically significant.